Catechol-O-methyltransferase (COMT), an enzyme that has a physiological role in the inactivation of adrenergic catecholamines and in the detoxification of xenobiotic amines, is generally regarded as a soluble cytoplasmic enzyme, but also known to exist as bound form in membrane structures. The soluble COMT has recently been shown to exist as two distinct molecular forms, designated COMT I and COMT II, which differ in their molecular size (MW 24,000 vs. Mw 47,500). The membrane-bound COMT, however, has received little attention. A line of recent pharmacological evidence, however, suggests that the membrane-bound COMT interacts with beta-adrenergic receptor (BAR) in the plasma membrane and its activity regulated by its interaction with the receptor by a mechanism independent of adenylate cyclase activation and cAMP production. In order to document the COMT-BAR interaction in the plasma membrane, our research objectives will be directed toward (1) the subcellular localization of membrane-bound COMT and BAr, (2) the characterization of membrane-bound COMT with respect to molecular and physicochemical properties, (3) the clarification of the relationship between membrane-bound and soluble COMT's, and (4) the study of the nature of COMT-BAR interaction by physicochemical techniques.